A new article in the Canadian Medical Association Journal has reported on a careful analysis of the published literature underlying current guidelines on the use of repetitive PSA testing to monitor risk for progression in men receiving first-line treatment for localized prostate cancer. Many patients may be surprised just how few data there are to support this extremely common clinical practice.
Dinnes et al. set out to determine the extent to which recommendations for repetitive monitoring of PSA levels to detect recurrent prostate cancer actually met established scientific criteria that should inform rule-based strategies for disease monitoring. The full text of this paper is available on line for the interested reader.
The authors identified a total of seven sets of clinical guidelines and two “statements of best practice” from nine organizations (four in North America, four in Europe and one in Australia). They then reviewed these guidance documents with care against the standard Appraisal of Guidelines for Research and Evaluation Framework.
The bottom line to their findings was pretty straightforward:
- There is “considerable inconsistency” in recommendations for use of PSA testing to monitor men after first-line therapy.
- Recommendations on when to test are largely based on “standard” follow-up schedules that have little scientific basis.
- Recommendations on when to take further therapeutic action are based on consensus statements or on retrospective case series.
- Eight of the nine guidance documents recognize “the potential presence of measurement variability,” but make no attempt to address the impact of such variability on the interpretation of results of sequential PSA tests.
- Recommendations are often made with few or no supporting references.
- Of 48 papers cited as sources for recommendations, 14/48 (29 percent) were review articles and 34/48 (71 percent) were primary studies.
The findings of this study, again, come as no great surprise to long-time watchers of the prostate cancer world. There is little evidence for and no consistency about a whole variety of issues that underlie the question of how best to determine real recurrence of prostate cancer after first line treatment.
Here are just some of the questions to which we do not, actually, have good, science-based — as opposed to opinion-based — answers (and they certainly aren’t the only ones):
- What should a man’s PSA level be after whole gland surgery administered with curative intent today (e.g., < 0.1 or < 0.01 ng/ml)?
- What should a man’s PSA level be after radiation therapy admininistered with curative intent today (i.e., what is a truly acceptable nadir PSA level)?
- What is the correct way to determine recurrence after surgery (e.g., a rise in the PSA level to ≥ 0.2 ng/ml or a PSA rise to ≥ 0.1 ng/ml with a doubling time of < 15 months)?
- Are either the Phoenix criteria or the ASTRO criteria really accurate ways to assess recurrence after radiation therapy?
- What should trigger initiation of salvage treatment for a man with recurrence after surgery?
- What should trigger initiation of salvage treatment for a man with recurrence after first-line radiation therapy?
Obviously, there are no “one size fits all” answers to these questions. A 48-year-old man with a recurrence 9 months after first-line surgery for localized disease characterized by a PSA of 2.7 ng/ml and 2/12 small positive biopsy cores, one of which contained 5 percent of Gleason 9 prostate cancer, is at a very different long-term risk level than a man of 81 years with a small rise in his PSA a decade after first-line radiation therapy for localized disease characterized by a PSA of 4.8 and 4/12 positive biopsy cores all containing Gleason 6 disease.
The truth, however, is that we still, really don’t have scientifically established guidelines for assessing and managing the recurrence of prostate cancer, and we don’t have this type of guidaance because we don’t have data to support it.